Co-exposure of nanoplastics and arsenic causes neurotoxicity in zebrafish (Danio rerio) through disrupting homeostasis of microbiota-intestine-brain axis.

ABSTRACT

Nanoplastics (NPs) and arsenic (As) are toxic pollutants prevalent on the earth and have gained considerable attention in recent decades. Although numerous studies reported NPs and As can cause neurotoxicity there are still significant knowledge gaps in illustrating their combined toxicity and its mechanism. In this study, the co-exposure of environmentally relevant concentrations of NPs and As caused neurobehavioral toxicity in zebrafish, as evidenced by reduced swimming ability, anxiety and impaired short-term learning memory. Potentially, its toxicity mechanism is through disrupting the homeostasis of microbiota-intestine-brain axis in zebrafish. Specifically, the co-exposure reduced the 5-hydroxytryptamine (5-HT) production in intestine, which led to lower levels of 5-HT transported by the blood circulation to the brain. Ultimately, neurobehavior was adversely affected by the reduced binding of 5-HT to its receptors. Intestine, the primary source of 5-HT, its impaired health (aggravation in oxidative stress, mitochondrial damage and histopathological alterations) induced the dysregulation in the 5-HT system, which may be induced by the increased accumulation of As in the intestine by the co-exposure. Besides, the reduced 5-HT levels were correlated with decreased Firmicutes and Protecbacteria and increased Actinobacteriota and Chloroflexi in intestines. Potentially, intestinal microbiota adversely regulates the intestine-brain axis by reducing SCFAs levels. Thus, the alteration of intestinal microbiota structure may be the other reason for the dysregulation of intestine-brain axis. In summary, co-exposure of NPs and As induced neurobehavior toxicity probably through disrupting the homeostasis of microbiota-intestine-brain axis. This study provides insights into assessing the environmental health risks of the pollution of NPs and As to aquatic organisms.